The present invention relates to methods of treating hemorrhoids and diseases of the anorectum employing novel pharmaceutical compositions. In particular, the present invention relates to topical applications of hyaluronate preparations as rectal bonding and adhesion agents, anti-inflammatory agents and bio-repair materials. The use of hyaluronate preparations employs their properties to reduce the inflammation, pain, swelling, and sequelae of injured, irritated, diseased, strained, or traumatized anorectal tissues while adhering to and protecting sensitive tissues of the anorectum. The source of the hyaluronate used in the treatment compositions may be a hyaluronic acid or any acceptable salt form of hyaluronic acid. The term "hyaluronate" is often used to mean "hyaluronic acid equivalent" which equates to hyaluronic acid of varying molecular weights and any of their salt forms.
Hyaluronic acid is a naturally occurring mucopolysaccharide with a molecular weight generally ranging between about 50,000 and 8,000,000 (or possibly higher), depending on the sources of the hyaluronate and the analytical methods used in its determination.
Methods of obtaining highly-pure or ultra-pure hyaluronic acid and its salt forms, isolation techniques, and analytical methods for testing purity are provided, for example, in the U.S. Pat. Nos. 3,396,081, 4,141,973, 4,517,295, 4,736,024, 4,784,990 and 4,808,576.
Hyaluronic acid is well known, being found in the joint tissue and vitreous humor of the eyes of mammals. It has been extracted from rooster combs, human umbilical cords and bacterial cultures such as those of hemolytic group A and C streptococci for various therapeutic purposes. One of the first therapeutic uses of this material was as a replacement for the liquid vitreous of the human eye to aid in ophthalmic surgery, especially in the treatment of retinal detachment. It has also been used for the relief of trauma or irritation in joint tissue of mammals including humans by injection into the synovial fluid of the joint.
An extensive discussion of its various uses is found in U.S. Pat. No. 4,141,973. The administration of hyaluronic acid alone and with cortisone in various animal joints, especially horses, is discussed in the article by Rydell et al., "Effect of Intra-articular Injection of Hyaluronic Acid on the Clinical Symptoms of Osteoarthritis and on Granulation Tissue Formation", Clinical Orthopaedics and Related Research, October, 1971, No. 80. The use of hyaluronic acid in human joints is reported in the "Preliminary Clinical Assessment of Na Hyaluronate Injection into Human Arthritic Joints" by Peyron et al., Pathologic Biologic, October, 1974, Vol. 22, No. 8. The use of hyaluronic acid in reducing fibrotic wound reactions is reported in the article by Rydell, "Decreased Granulation Tissue Reaction After Installment of Hyaluronic Acid", Acta Orthop. Scandinav, Vol. 41.
Hyaluronic acid and derivatives thereof can play a critical role in wound healing. Hyaluronate preparations are already marketed by several companies as products utilized in eye surgery, hip repair, dentistry, cosmetics, skin treatments, and dermatology.
U.S. Pat. No. 4,736,024 describes the use of hyaluronic acid or a molecular weight fraction thereof as a vehicle for pharmacologically active substances. The vehicle may be in suppository form for transcutaneous absorption to obtain a systemic effect. In contrast, the present methods of treatment employ the bonding, protective, healing, therapeutic, and curative properties of hyaluronic acid and derivatives thereof for their direct, local therapeutic affect when applied topically to thrombosed anorectal vessels, inflamed tissues of the anorectum, rectal fissures, and/or pruritis ani. In the present invention, hyaluronic acid (and its derivatives) is the active pharmaceutical agent.
For the present invention, pharmaceutical preparations containing less than 0.1% to more than 25.0% hyaluronate have been made and applied topically to the anorectum in successfully relieving the tenderness, soreness, pain, burn, itch, and discomfort of inflamed, irritated anorectal tissues. Hyaluronate reduces pain, inflammation, and swelling due to its anti-inflammatory and membrane stabilizing properties. Hyaluronate protects sensitive tissues and vessels of the anorectal epithelium and rectal mucosa by adhering to them and can remarkably mask the trauma of inflamed tissues.